This competing renewal seeks continued funding for The Jackson Laboratory's (TJL) Induced Mutant Resource (IMR) to continue to provide this critical resource of genetically engineered mice to the scientific community. Selectively altering the mouse genome by gene transfer (transgenic mice), homologous recombination and temporal- and tissue-specific gene mutation (gene targeting), and chemical mutagenesis is providing new and powerful tools for biomedical research. The production and use of such mice has rapidly expanded, increasing the need for resource centers to maintain, preserve, and distribute them at a high health status and as free from legal restrictions as possible. Researchers frequently receive so many requests for their mice that they must be relieved of the burden that distributing mice places on their research programs and grants. TJL has maintained and distributed mutant strains of mice for over 50 years. In 1992, TJL established the IMR whose purpose is to import, cryopreserve, and distribute biomedically important induced mutant mice. The need for the IMR is evidenced by its rapid growth. Since it began, the IMR has accepted >950 mutant stocks, of which >300 are still being distributed from the breeding colony. The remaining strains have been archived as frozen embryos or sperm. Another 120 are currently in the importation process. In the first 4.5 years of the current grant period, the IMR distributed >450,000 mice; in 2002 mice were distributed to 750 investigators and supported research funded by nearly every NIH categorical institute. We request support for rederivation, cryopreservation, and strain development to improve the scientific value of IMR strains; mice are maintained for distribution to other scientists on as much of a cost recovery basis as possible. To improve the IMR resource program we propose to do research to (1) develop more reliable methods of sperm cryopreservation and recovery, (2) characterize the tissue- and organ-specific expression of Cre-expressing strains by using appropriate reporter strains already present in the IMR, and (3) carry out further phenotype characterization of selected mutants to enhance their value. IMR acceptance of strains is coordinated with the NCRR-funded Mutant Mouse Regional Resource Centers (MMRRC), the National Cancer Institute Mouse Models of Human Cancer Consortium (MMHCC), and the European Mutant Mouse Archive (EMMA) to avoid duplication of resources.